We have suggested that gamma-aminobutyric acid (GABA) in the hypothalamus plays a tonic inhibitory role in the control of the luteinizing hormone (LH) release in intact male rats. To assess whether feedback from the testis alters the inhibitory GABAergic tone in the medial preoptic area (MPO) of male rats, an in vivo microdialysis study was performed in gonadally intact (n = 10), castrated (n = 12) and castrated testosterone-primed (n = 10) male rats. The microdialysis samples were collected and sequential blood samples were also obtained at 1-hour intervals. GABA in the dialysate was determined by high-performance liquid chromatography system and serum LH concentration was determined by radioimmunoassay. Episodic GABA release in the MPO was observed in all three groups of male rats, although castrated male rats showed lower GABA release (2.3 ± 0.3 ng/h) than intact and castrated testosterone-primed male rats (4.0 ± 0.5 and 4.6 ± 1.0 ng/h, respectively). Conversely, castrated male rats showed higher serum LH concentration (7.31 ± 0.46 ng/ml) than intact and castrated testosterone-primed male rats (0.71 ± 0.04 and 0.53 ± 0.07 ng/ml, respectively). In addition, intravenous infusion of bicuculline significantly increased serum LH in intact male rats, whereas bicuculline did not alter serum LH concentrations in castrated male rats. These results are consistent with the hypothesis that the feedback of testosterone stimulates GABA release in the region of the GnRH cell bodies and dendrites in male rats.

Bilger M, Heger S, Brann DW, Paredes A, Ojeda SR: A conditional tetracycline-regulated increase in gamma amino butyric acid production near luteinizing hormone-releasing hormone nerve terminals disrupts estrous cyclicity in the rat. Endocrinology 2001;142:2102–2114.
Funabashi T, Jinnai K, Kimura F: Bicuculline infusion advances the timing of Fos expression in LHRH neurons in the preoptic area of proestrous rats. NeuroReport 1997;8:771–774.
Jarry H, Hirsch B, Leonhardt S, Wuttke W: Amino acid neurotransmitter release in the preoptic area of rats during the positive feedback actions of estradiol on LH release. Neuroendocrinology 1992;56:133–140.
Kimura F, Funabashi T: Two subgroups of gonadotropin-releasing hormone neurons control gonadotropin secretion in rats. News Physiol Sci 1998;13:225–231.
Mitsushima D, Hei DL, Terasawa E: γ-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty. Proc Natl Acad Sci USA 1994;91:395–399.
Sim JA, Skynner MJ, Pape JR, Herbison AE: Late postnatal reorganization of GABAA receptor signaling in native GnRH neurons. Eur J Neurosci 2000;12:3497–3504.
He D, Mitsushima D, Uemura T, Hirahara F, Kimura F: Change in the number of GABAA receptor positive GnRH neurons in immature and mature male rats. Jpn J Physiol 2000;50(suppl):S203.
Jung H, Shannon EM, Fritschy JM, Ojeda SR: Several GABAA receptor subunits are expressed in LHRH neurons of juvenile female rats. Brain Res 1998;780:218–229.
Petersen SL, McCrone S, Coy D, Adelman JP, Mahan LC: GABAA receptor subunit mRNAs in cells of the preoptic area: Colocalization with LHRH mRNA using dual-label in situ hybridization histochemistry. Endocrine 1993;1:29–34.
Horvath TL, Naftolin F, Leranth C: Luteinizing hormone-releasing hormone and gamma-aminobutyric acid neurons in the medial preoptic area are synaptic targets of dopamine axons originating in anterior periventricular areas. J Neuroendocrinol 1993;5:71–79.
Leranth C, MacLusky NJ, Sakamoto H, Shanabrough M, Naftolin F: Glutamic acid decarboxylase-containing axons synapse on LHRH neurons in the rat medial preoptic area. Neuroendocrinology 1985;40:536–539.
Witkin JW: Increased synaptic input to gonadotropin-releasing hormone neurons in aged, virgin, Sprague-Dawley rats. Neurobiol Aging 1992;13:681–686.
Mitsushima D, Tin-Tin-Win-Shwe, Funabashi T, Shinohara K, Kimura F: GABA release in the medial preoptic area of cyclic female rats. Neuroscience 2002;113:109–114.
Mitsushima D, Tin-Tin-Win-Shwe, Kimura F: γ-Aminobutyric acid release in the medial preoptic area in cyclic female rats. Soc Neurosci Abstr 2001;27:630,2.
Davis AM, Grattan DR, Selmanoff M, McCarthy MM: Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: Implications for sexual differentiation. Horm Behav 1996;30:538–552.
Grattan DR, Selmanoff M: Sex differences in the activity of γ-aminobutyric acidergic neurons in the rat hypothalamus. Brain Res 1997;775:244–249.
Searles RV, Yoo MJ, He JR, Shen WB, Selmanoff M: Sex differences in GABA turnover and glutamic acid decarboxylase (GAD65 and GAD67) mRNA in the rat hypothalamus. Brain Res 2000;878:11–19.
Szwarcfarb B, Carbone S, Stein ML, Medina J, Moguilevsky JA: Sexual differences in the effect of the GABAergic system on LH secretion and in the hypothalamic ontogenesis of GABAA receptors in prepubertal rats. Brain Res 1994;646:351–355.
He D, Mitsushima D, Uemura T, Hirahara F, Funabashi T, Shinohara K, Kimura F: Effects of naloxone on the serum luteinizing hormone level and the number of Fos-positive gonadotropin-releasing hormone neurons in immature female rats. Brain Res 2000;858:129–135.
Mitsushima D, He D, Funabashi T, Shinohara K, Kimura F: Increase in the number of detectable preoptic GAD67 immunoreactive cells in immature male rats. Neurosci Res 2001;40:141–146.
Albe-Fessard D, Stutinsky F, Libouban S: Atlas Stéréotaxique du Diencéphale de Rat Blanc. Paris, Centre National de la Recherche Scientifique, 1966.
Kuczenski R, Segal DS, Cho AK, Melega W: Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci 1995;15:1308–1317.
Mitsushima D, Mizuno T, Kimura F: Age-related changes in diurnal acetylcholine release in the prefrontal cortex of male rats as measured by microdialysis. Neuroscience 1996;72:429–434.
Mitsushima D, Yamanoi C, Kimura F: Restriction of environmental space attenuates locomotor activity and hippocampal acetylcholine release in male rats. Brain Res 1998;805:207–212.
Mitsushima D, Jinnai K, Kimura F: Possible role of γ-aminobutyric acid-A receptor system in the timing of the proestrous luteinizing hormone surge in rats. Endocrinology 1997;138:1944–1948.
Frankfurt M, Fuchs E, Wuttke W: Sex differences in γ-aminobutyric acid and glutamate concentrations in discrete rat brain nuclei. Neurosci Lett 1984;50:245–250.
Pape JR, Skynner MJ, Sim JA, Herbison AE: Profiling γ-aminobutyric acid (GABAA) receptor subunit mRNA expression in postnatal gonadotropin-releasing hormone (GnRH) neurons of the male mouse with single cell RT-PCR. Neuroendocrinology 2001;74:300–308.
Chen WP, Witkin JW, Silverman AJ: Sexual dimorphism in the synaptic input to gonadotropin releasing hormone neurons. Endocrinology 1990;126:695–702.
Butcher RL, Collins WE, Fugo NW: Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrous cycle of the rat. Endocrinology 1974;94:1704–1708.
Smith MS, Freeman ME, Neill JD: The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: Prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinology 1975;96:219–226.
Ellis GB, Desjardins C: Male rats secrete luteinizing hormone and testosterone episodically. Endocrinology 1982;110:1618–1627.
Tin-Tin-Win-Shwe, Mitsushima D, Kimura F: Preoptic GABA release in castrated estrogen-primed rats. Jpn J Physiol 2001;51(suppl): S253.
Mitsushima D, Kimura F: The maturation of GABAA receptor-mediated control of luteinizing hormone secretion in immature male rats. Brain Res 1997;748:258–262.
Rettori V, Karara A, Narizzano OC, Ponzio R, McCann SM: The effect of bicuculline injected into the medial preoptic area on the release of prolactin (PRL) and luteinizing hormone (LH) in the rat. Neuroendocr Lett 1989;11:177–182.
Mitsushima D, Funabashi T, Kimura F: Fos expression in gonadotropin-releasing hormone neurons by naloxone or bicuculline in intact male rats. Brain Res 1999;839:209–212.
Grattan DR, Park SK, Selmanoff M: Orchidectomy and NMDA increase GnRH secretion as measured by push-pull perfusion of rat anterior pituitary. Am J Physiol 1995;268:E685–E692.
Sagrillo CA, Selmanoff M: Castration decreases single cell levels of mRNA encoding glutamic acid decarboxylase in the diagonal band of Broca and the sexually dimorphic nucleus of the preoptic area. J Neuroendocrinol 1997;9:699–706.
Yoo MJ, Searles RV, He JR, Shen WB, Grattan DR, Selmanoff M: Castration rapidly decreases hypothalamic γ-aminobutyric acidergic neuronal activity in both male and female rats. Brain Res 2000;878:1–10.
Zsarnovzky A, Horvath TL, Garcia-Segura LM, Horvath B, Naftolin F: Oestrogen-induced changes in the synaptology of the monkey (Cercopithecus aethiops) arcuate nucleus during gonadotropin feedback. J Neuroendocrinol 2001;13:22–28.
Poletti A, Negri-Cesi P, Rabuffetti M, Colciago A, Celotti F, Martini L: Transient expression of the 5α-reductase type 2 isozyme in the rat brain in late fetal and early postnatal life. Endocrinology 1998;139:2171–2178.
Grattan DR, Rocca MS, Sagrillo CA, McCarthy MM, Selmanoff M: Antiandrogen microimplants into the rostral medial preoptic area decrease γ-aminobutyric acidergic neuronal activity and increase luteinizing hormone secretion in the intact male rats. Endocrinology 1996;137:4167–4173.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.